Modeling yeast cell cycle

1. Modeling the cell cycle of S. cerevisiae with special focus on the G1-network to study the interplay of growth and division. Population simulations are performed to gain insight into the different effects that cell synchronization techniques like alpha factor arrest or elutriation have on the population structure. 2. Design of a self oscillating model of the complete cell cycle with predefined points for external interaction (like different stresses) and interaction points for other cellular processes or components like metabolism or the DNA replication machinery. This model can be used as a scaffold for combined simulations with other models.

METHODS

• ODE modeling

PEOPLE

 Dr. Friedemann Uschner       Stephan Adler       Ulrike Münzner

Understanding G1/S transition

Eukaryotic cell cycle is a highly ordered process controlled by cyclin-dependent kinases (CDKs) and their corresponding cyclins. We are focusing on the G1/S transition also called START in S. cerevisiae and known as the point of no return, meaning once cells pass this checkpoint they initiate DNA replication and have to pass through the entire cell cycle. To understand the regulation at START we use two different approaches. First, we combine single cell data and stochastic modeling and, secondly, we use a transcriptome-wide approach for deletion mutants of the main G1/S transition regulators to understand the importance of these regulators for cell cycle progression and periodic genes expression.   

METHODS

• RNA-FISH
• RNA-sequencing 

PEOPLE

 Julia Katharina Schlichting       Dr. Katja Tummler       Lotte Teufel       Stephan Adler

Understanding G2/M transition

We aim to understand how the initiation of mitosis is regulated. To this end, we test the hypothesis that localized translation of a single cell cycle regulator (cyclin) is a way for budding yeast cells to determine when the daughter cell is ready for independent life. There is evidence that the mRNA in question enriches in the daughter cell and a candidate system for the actin-mediated transport has been identified. We investigate the spatio-temporal dynamics of individual CLB2 mRNA in living cells using the MS2 system combined with various pre-commercial microscopes. Additionally, we are improving methods for the visualization of single mRNAs and proteins inside living cells.

METHODS

• live cell microscopy
• MS2 system
• single molecule fluorescence in situ hybridisation (smFISH)

PEOPLE

Severin Ehret

A comprehensive model of the cell division cycle control network

In this project, we formalize biochemical knowledge into a comprehensive mechanistic model of the cell division cycle of baker’s yeast, Saccharomyces cerevisiae.

The cell division cycle is the process through which one cell proliferates into two. It is one of the fundaments of life and highly relevant for health and disease. Cell division is strictly controlled by an intricate signaling system that synchronizes three different duplication events: DNA replication, nuclear division and cell division, hence ensuring ordered duplication and separation. Errors in this regulation may lead to cell death or genomic instability and consequently to severe diseases such as cancer. To understand the function of this system mechanistically in terms of biochemical reactions will be of fundamental importance to understand life - as well as to diagnose and treat diseases due to errors in this control network.

Based on a comprehensive literature review, we encode a detailed mechanistic model in the rxncon language. We use an iterative workflow of literature curation, visualization and bipartite Boolean simulation to build, validate and debug the network model. In the end, we use parameter-free simulation to analyse the predicted phenotype of both deletion and point mutations.

METHODS

• Reaction-contingency based modeling
• Boolean modeling

PEOPLE

Prof. Edda Klipp       Dr. Marcus Krantz       Ulrike Münzner